DESCRIPTION: Globally, an estimated 322,000 individuals die from fire-related burn injuries each year. In the United States, 450,000 experience burns requiring hospitalization and 3,500 of these lead to fatal outcomes. A burn of 30% of total body area can cost as much as $200,000 in initial hospitalization costs, not including the additional costs for repeat admission for reconstruction and for rehabilitation. The economic impact of these injuries extends far beyond the cost on the nation's healthcare system to include loss of wages, costs relating to deformities, and emotional trauma. The primary goal of this application is to evaluate the efficacy of Novan's nitric oxide (NO)-releasing topical gel formulation against thermal and chemical burns. Novan believes this research will demonstrate that topically applied nitric oxide provides a breakthrough regenerative medicine strategy based on the body's natural process of wound repair. Nitric oxide has been shown in the body to reduce inflammation, promote new blood vessel formation, and facilitate granulation tissue formation. Unfortunately, the challenges associated with the storage and controlled delivery of nitric oxide has limited the development of NO-based topical therapeutics. Novan Inc.'s NO- releasing silica nanoparticle technologies (Nitricil) overcomes the delivery issues associated with other nitric oxide storage methods. Specifically Novan aims to test Novan's lead anhydrous topical gel formulation in a hybrid second-degree burn wound model, developed by United States Army Military Research Institute for Chemical Defense, and quantify the rates of re-epithelialization and inflammation via histological and biophysical techniques; and explore the stability of the anhydrous gel at temperature conditions ranging from 5 to 40 C, assessing both potency and quantification of degradation products as a function of time and temperature. The outcome of this 6-month Phase I SBIR grant will provide comparative data on the healing benefits of topically applied nitric oxide in thermal and sulfur mustard (HD) burns. The results will be the first in vivo application of nitric oxide to mitigate HD injury and the first study of Nitricil in thermal burns.In Phase II, Novan will further define the dose-response relationship between nitric oxide and the thermal/HD wound healing progression, as well as, explore the full dermal toxicology/pharmacokinetics of the NO-based therapy. PUBLIC HEALTH RELEVANCE: Globally, an estimated 322,000 individuals die from fire-related burn injuries each year. In the United States, 450,000 individuals seek medical care each year for burns. Approximately 45,000 experience burns requiring hospitalization and 3,500 of these lead to fatal outcomes. The economic impact of these injuries extends far beyond the cost on the nation's healthcare system to include loss of wages; costs relating to deformities; and emotional trauma. The use of exogenous nitric oxide therapy for the mitigation of burn injuries is extraordinarily promising. Novan believes this research will demonstrate that topically applied nitric oxide reduces burn wound inflammation and accelerates re-epithelialization, providing a regenerative medicine strategy based on the body's natural process of wound repair.